The present invention, in some embodiments thereof, relates to nanomaterials and, more particularly, but not exclusively, to self-assembled nanostructures composed of a plurality of dipeptides, to processes of generating same and to uses thereof.
Over the last few decades, molecular self-assembly has served as a cornerstone for the production of novel materials, which have already been incorporated into various applications in the fields of material science, electrical engineering and medicine. The ability to design basic building blocks which form self-assembly products with desired properties, in a bottom-up manner, has greatly promoted novel applications derived from such materials. In particular, the field of supramolecular polymers has gained much interest due to their ability to bridge the gap between covalent polymers and species formed by bottom-up self-assembly processes. The combination of supramolecular chemistry and polymer science has given rise to a rich diversity of supramolecular polymer nano- and micro-structures over the past two decades, including tubes, fibers, rods, films, plates, hydrogels, nanocages and vesicles.
The dynamic nature of the non-covalent interactions formed throughout the process of supramolecular polymers self-assembly enhance the ability to spatially and temporally control the formed end-product architectures. Furthermore, the unique molecular organization can be influenced by external stimuli, such as pH, temperature and the introduction of organic solvents. These stimuli may serve to alter the unique properties and characteristics of the formed non-covalent molecular polymers.
Similar to the well-studied covalent polymers, through the incorporation of two or more different building blocks, supramolecular co-polymers can be produced. As in the elongation of co-polymers, also in the case of supramolecular co-polymers, the incorporation of multiple building blocks significantly increases the chemical diversity and conformational space of available polymers. Peptide building blocks feature biocompatibility, chemical flexibility and versatility, biological recognition abilities and facile synthesis, and therefore serve as attractive organic building block for bionanotechnology applications.
Short aromatic peptides, particularly aromatic dipeptides such as the diphenylalanine aromatic core of the β-amyloid polypeptide, have been shown to undergo self-assembly to form well-ordered hollow tubular nanostructures in aqueous solution [Reches M, Gazit E. Science 2003; 300: 625-627]. These self-assembled aromatic dipeptide nanostructures have remarkable chemical and thermal stability and extraordinary mechanical strength [Sedman et al. J. Am. Chem. Soc. 2006; 128: 6903-6908; Adler-Abramovich et al. Langmuir 2006; 22: 1313-1320].
The self-assembly of aromatic dipeptide nanostructures has been performed by horizontal and vertical alignment of nanostructures and a controlled self-assembly has also been obtained using enzymatic activation of self-immolative dendrimers [Reches and Gazit E. Nat. Nanotechnol. 2006; 1:195-200; Adler-Abramovich et al. ChemBioChem 2007; 8: 859-862].
Aromatic dipeptide nanostructures where shown to serve as a degradable mold for the fabrication of silver nanowires, as a scaffold for the organization of platinum nanoparticles and as a template for the formation of coaxial nanocables [Carny et al. Nano Lett. 2006; 6: 1594-1597; Song et al. Chem. Commun. 2004; 9:1044-1045].
Peptide tubular nanostructures were also used for the fabrication of sensitive electrochemical biosensors, and for the formation of biocompatible hydrogels [Yemini et al. Anal. Chem. 2005; 77: 5155-5159; Yemini et al. Nano Lett. 2005; 5: 183-186; Mahler et al. Adv. Mater. 2006; 18: 1365-1370].
WO 2004/052773 and WO 2004/060791 disclose self-assembled peptide tubular nanostructures made of short aromatic peptides, and their use as, for example, a casting mold for metal nanowires, for the fabrication of peptide-nanotube platinum-nanoparticle composites, and in electrochemical biosensing platforms.
WO 2007/0403048 and Reches and Gazit [Isr. J. Chem. 2005; 45: 363-371] discloses the assembly of tubular and fibrillar (amyloid-like) structures by non-charged, end-capping modified aromatic peptides and, particularly, by diphenylalanine analogs such as, for example, Boc-Phe-Phe-OH and Fmoc-Phe-Phe-OH peptides.
Adler-Abramovich et al. [J. Pept. Sci. 2008; 14: 217-223] describe that two types of nanostructures; nanotubes and nanospheres; are obtained by the self-assembly of the aromatic dipeptide Phe-Phe, while using different end-capping moieties. Spherical nanotubes are self-assembled while using tertbutoxycarbonyl-Phe-Phe-OH (Boc-Phe-Phe-OH), and fibrillar nanostructures are self-assembled while using Fmoc-Phe-Phe-OH. It has been shown that both spherical and tubular structures could be efficiently used as an ‘ink’ and patterned on transparency foil and ITO plastic surfaces using a commercial inkjet printer.
It has recently been shown that the co-assembly of short peptide building blocks can produce complex architectures such as “beads on a string”, hydrogels and tubes. This co-assembly into supramolecular co-polymers allows modulation of the architecture and the physical and mechanical properties of such ultra-structures. See, for example, Orbach et al. Langmuir 2012, 28, 2015-2022; Carny et al. Nano Lett. 2006, 6, 1594-7.
Sedman et al. [J. of Microscopy, 2013, pp. 1-8] teach nano- and micro-scale fibrillar and tubular structures formed by mixing two aromatic dipeptides, Phe-Phe and D-Nal-Nal, and describe that the mechanical properties of the structures depend on the percentage of each peptide in the mixture.
Yuran et al. [ACS Nano, 2012, 6 (11), pp 9559-9566] describes the formation of complex peptide-based structures by the co-assembly of Phe-Phe-OH and Boc-Phe-Phe-OH, into a construction of beaded strings, where spherical assemblies are connected by elongated elements.
Maity et al. [J. Mater. Chem. B, 2014, 2, 2583-2591] describes the co-assembly of two aromatic dipeptides, diphenylalanine and Fmoc-L-DOPA(acetonated)-D-Phe-OMe, into different spherical structures that are similar in morphology to either red or white blood cells.